It is particularly preferred to employ candidal genes and gene products as targets for the development of antifungals. Candida spp. make up a medically important genus of microbes. They are known to produce two main types of infection, superficial infections of the mucosa and skin, and systemic infections, particularly in immuno-compromised patients, characterized by dissemination to the body tissues with poor prognosis without intervention. C. albicans is the principal species causing candida infections.
The frequency of Candida albicans infections has risen dramatically in the past 20 years. This has been attributed to an increasing population of people with weakened immune systems and the use of broad spectrum antibacterials and more interventional surgical practices. The amoury of good antifungal agents is small and resistance to existing agents is an emerging problem. This has created a demand for both new antifungal agents and diagnostic tests for this organism.
Fungi like bacteria and plants, but unlike mammals, are able to synthesize the aromatic amino acids phenylalanine, tyrosine and tryptophan. In fungi, a single polypeptide, the arom multifunctional enzyme, catalyses five consecutive reactions of the central aromatic biosynthetic pathway (Lambert et al. (1985). The 3-dehydroquinate synthase activity of the pentafunctional arom enzyme complex of Neurospora crassa is Zn.sup.2+ -dependent. Biochemical Journal 226:817-29. Duncan et al. (1987). The pentafunctional arom enzyme of Saccharamyces cerevisiae is a mosaic of monofunctional domains. Biochemical Journal 246:375-86.). Inhibition of any step catalyzed by this enzyme will prevent the synthesis of aromatic amino acids, p-aminobenzoic acid (precursor for folate) and ubiquinone. These essential metabolites are in limiting concentrations in mammalian tissues and thus inhibition of this enzyme is a valid antifungal strategy.
Clearly, there is a need for factors that may be used to screen compounds for antifungal activity and which may also be used to determine their roles in pathogenesis of infection, dysfunction and disease. There is a need, therefore, for identification and characterization of such factors which can play a role in preventing, ameliorating or correcting infections, dysfunctions or diseases.
The polypeptide of the present invention has the conserved residues, and have amino acid sequence homology to known arom multifunctional protein protein.